摘要
目的研究二氢杨梅素(Dihydromyricetin,DHM)对阿尔茨海默病(Alzheimer’s disease,AD)模型小鼠脑内肿瘤坏死因子α(TNF-α)及小胶质细胞M1、M2表型转化的影响。方法在体外实验中,以20μg/ml Aβ_(1-42)刺激BV2细胞24 h诱导其活化,通过2.5μg/ml DHM及等质量浓度的DMSO稀释液干预BV2细胞24 h,分别作为治疗组和对照组,采用免疫印迹法(Western blot)检测炎症因子TNF-α、小胶质细胞M1和M2表型的表达水平。在动物实验中,取4月龄的APP/PS1双转基因模型小鼠10只,按随机数字表法平均分为DHM治疗组和对照组。DHM治疗组小鼠腹腔注射DHM 1 mg/(kg·d),对照组小鼠腹腔注射等量经生理盐水稀释的DMSO溶液,连续治疗2周。采用Western blot检测2组小鼠脑内炎症因子TNF-α的表达水平,用免疫荧光染色观察2组小鼠脑内M1、M2型小胶质细胞表型的表达情况。结果与对照组比较,DHM治疗抑制BV2细胞释放TNF-α,减少APP/PS1小鼠脑内炎症因子TNF-α的表达,可明显减少诱导型一氧化氮合酶(i NOS)的表达水平,增加精氨酸酶1(Arginase-1)的表达。结论 DHM可有效抑制APP/PS1转基因小鼠脑内的炎症反应,其机制可能与DHM促进M1型小胶质细胞向M2型转化有关。
This study performed to observe the effect of dihydromyricetin（DHM） on the phenotypes ofmicroglia activation and the generation of inflammatory molecules in APP/PS1 double transgenic mice. In this study,BV2 cells and APP/PS1 double transgenic mice were employed. Western blot was used to observe the expression ofTNF-α in APP/PS1 mice and BV2 cells, while M1 and M2 phenotypes of microglia were detected by theimmunofluorescence staining and Western blotting. Data showed that compared with control groups, DHM treatmentcould significantly reduce the expression levels of TNF-α, inhibit the expression of nitric oxide synthase（i NOS） andup-regulate arginase-1（Arg-1）, which suggesting that DHM may be converting M1 into M2 phenotypes. Inconclusion, DHM can inhibit the inflammatory response in APP/PS1 double transgenic mice, and the mechanismmay be associated with the transformation of inflammatory M1 microglia to anti-inflammatory M2 cells.
出处
《免疫学杂志》
CAS
CSCD
北大核心
2017年第4期301-305,共5页
Immunological Journal
基金
教育部"新世纪优秀人才"支持计划(NCET-11-1084)
